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Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells.

Shen H, Shi S, Zhang Z, Gong T, Sun X - Theranostics (2015)

Bottom Line: First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not.In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events.These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.

ABSTRACT
Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44(+) cells in vitro. In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

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A) Photographs of B16F10-CD44+-bearing lungs on the day 24 after six consecutive intravenous injections of the indicated preparations. B) Enhanced antitumor effects of HA-SLNs/PTX based on tumor-bearing lung weight (n = 5). C) Histological staining of the tumor-bearing lungs tissue after treatment with HA-SLNs/PTX. Arrows, tumor nodules. D) Survival analysis of tumor-bearing mice (n = 7). *p < 0.05, **p < 0.01, compared with the group treated with HA-SLNs/PTX.
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Figure 8: A) Photographs of B16F10-CD44+-bearing lungs on the day 24 after six consecutive intravenous injections of the indicated preparations. B) Enhanced antitumor effects of HA-SLNs/PTX based on tumor-bearing lung weight (n = 5). C) Histological staining of the tumor-bearing lungs tissue after treatment with HA-SLNs/PTX. Arrows, tumor nodules. D) Survival analysis of tumor-bearing mice (n = 7). *p < 0.05, **p < 0.01, compared with the group treated with HA-SLNs/PTX.

Mentions: The antitumor efficacy of PTX-loaded HA-SLNs was tested in a murine lung metastasis model; animal survival as well as tumor weight and histopathology were analyzed. Obvious tumors were detected in the lungs of animals treated with PTX (commercial PTX injection) or SLNs/PTX, but not in animals treated with HA-SLNs/PTX (Fig. 8A and 8C); similarly, average lung weight was significantly lower in mice treated with HA-SLNs/PTX than in the PBS and PTX groups (p < 0.01). While animals treated with PBS died relatively rapidly, animals treated with PTX, PTX-loaded SLNs or PTX-loaded HA-SLNs survived significantly longer (log-rank test, p< 0.01; Fig. 8D). Six consecutive injections of PTX-loaded HA-SLNs led to substantially longer lifespan than the equivalent doses of PTX (p = 0.032, log-rank test) or PTX-loaded SLNs (p = 0.049, log-rank test)


Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells.

Shen H, Shi S, Zhang Z, Gong T, Sun X - Theranostics (2015)

A) Photographs of B16F10-CD44+-bearing lungs on the day 24 after six consecutive intravenous injections of the indicated preparations. B) Enhanced antitumor effects of HA-SLNs/PTX based on tumor-bearing lung weight (n = 5). C) Histological staining of the tumor-bearing lungs tissue after treatment with HA-SLNs/PTX. Arrows, tumor nodules. D) Survival analysis of tumor-bearing mice (n = 7). *p < 0.05, **p < 0.01, compared with the group treated with HA-SLNs/PTX.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402499&req=5

Figure 8: A) Photographs of B16F10-CD44+-bearing lungs on the day 24 after six consecutive intravenous injections of the indicated preparations. B) Enhanced antitumor effects of HA-SLNs/PTX based on tumor-bearing lung weight (n = 5). C) Histological staining of the tumor-bearing lungs tissue after treatment with HA-SLNs/PTX. Arrows, tumor nodules. D) Survival analysis of tumor-bearing mice (n = 7). *p < 0.05, **p < 0.01, compared with the group treated with HA-SLNs/PTX.
Mentions: The antitumor efficacy of PTX-loaded HA-SLNs was tested in a murine lung metastasis model; animal survival as well as tumor weight and histopathology were analyzed. Obvious tumors were detected in the lungs of animals treated with PTX (commercial PTX injection) or SLNs/PTX, but not in animals treated with HA-SLNs/PTX (Fig. 8A and 8C); similarly, average lung weight was significantly lower in mice treated with HA-SLNs/PTX than in the PBS and PTX groups (p < 0.01). While animals treated with PBS died relatively rapidly, animals treated with PTX, PTX-loaded SLNs or PTX-loaded HA-SLNs survived significantly longer (log-rank test, p< 0.01; Fig. 8D). Six consecutive injections of PTX-loaded HA-SLNs led to substantially longer lifespan than the equivalent doses of PTX (p = 0.032, log-rank test) or PTX-loaded SLNs (p = 0.049, log-rank test)

Bottom Line: First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not.In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events.These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China.

ABSTRACT
Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44(+)) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44(-)) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44(+) cells in vitro. In the B16F10-CD44(+) lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy.

Show MeSH
Related in: MedlinePlus